CORRESPONDENCE

Injury can trigger an acute inflammatory re-sponse, even in the absence of concomitant infection. “Sterile ” inflammation is also associ-ated with several types of cancer. Two events are key for the development of sterile inflammation: the recruitment of leukocytes, especially neu-trophils and monocytes, and their activation to release proinflammatory cytokines. High-mobility group box 1 (HMGB1) is a nuclear protein that signals tissue damage when released into the extracellular medium, and thus works as a damage-associated molec-ular pattern (DAMP; Bianchi, 2007). Extracel-lular HMGB1 can act both as a chemoattractant for leukocytes and as a proinflammatory media-tor to induce both recruited leukocytes and resi-dent immune cells to release TNF, IL-1, IL-6, and other cytokines. Notably, immune cells se-crete HMGB1 when activated by infection or tissue damage (Andersson and Tracey, 2011); mesothelioma and other cancer cells secrete HMGB1 constitutively (Jube et al., 2012). Recent studies have shown that the pro-inflammatory cytokine-stimulating activity of HMGB1 depends on the redox state of three cys-teines: C23 and C45 must form a disulfide bond within the first HMG-box domain of HMGB1, BoxA, whereas the unpaired C106 within BoxB must be in the thiol state (Yang et al., 2012)